Trial Outcomes & Findings for Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial (NCT NCT04049097)

NCT ID: NCT04049097

Last Updated: 2023-09-15

Results Overview

The Inclusion Body Myositis Functional Rating Scale (IBMFRS) includes 10 measures (swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, changing position from sitting to standing, walking, and climbing stairs), each graded on a Likert scale from 0 (being unable to perform) to 4 (normal). The sum of the 10 items gives a value between 0 and 40. A higher score represents less functional limitation. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 121 participants
• Primary outcome timeframe: Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).
• Results posted on: 2023-09-15

Participant Flow

Participant milestones

Measure	Arimoclomol (Open-label) Arimoclomol base 248 mg 3 times daily (planned duration 40 months; actual duration after early termination of the trial approx. 28 weeks).
Overall Study STARTED	121
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	121

Reasons for withdrawal

Measure	Arimoclomol (Open-label) Arimoclomol base 248 mg 3 times daily (planned duration 40 months; actual duration after early termination of the trial approx. 28 weeks).
Overall Study Adverse Event	18
Overall Study Death	2
Overall Study Lost to Follow-up	1
Overall Study Physician Decision	2
Overall Study Withdrawal by Subject	9
Overall Study Protocol Violation	2
Overall Study Other	1
Overall Study The trial was terminated early by the sponsor	86

Baseline Characteristics

Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial

Baseline characteristics by cohort

Measure	Arimoclomol (Open-label) n=121 Participants Arimoclomol base 248 mg 3 times daily
Age, Continuous	66.2 years STANDARD_DEVIATION 7.91 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	98 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized White	115 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants
Age at diagnosis	62.3 years STANDARD_DEVIATION 8.02 • n=5 Participants

PRIMARY outcome

Timeframe: Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).

Population: Patients in the modified intention-to-treat population with data for IBMFRS at the early termination visit

The Inclusion Body Myositis Functional Rating Scale (IBMFRS) includes 10 measures (swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, changing position from sitting to standing, walking, and climbing stairs), each graded on a Likert scale from 0 (being unable to perform) to 4 (normal). The sum of the 10 items gives a value between 0 and 40. A higher score represents less functional limitation.

After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively.

Outcome measures

Measure	Arimoclomol (Open-label) n=106 Participants Arimoclomol base 248 mg 3 times daily
Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score	-1.7 score on a scale Standard Deviation 2.60

SECONDARY outcome

Timeframe: Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).

Population: Patients in the modified intention-to-treat population with data for the Six Minutes Walking distance test at the early termination visit

Patients were instructed to walk down one side of a track and back along the opposite side as quickly and safely as possible for 6 minutes. Patients were allowed to take breaks as needed during the walking period, but timing continued during breaks. The distance walked in meters was recorded after 6 minutes.

After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively.

Outcome measures

Measure	Arimoclomol (Open-label) n=74 Participants Arimoclomol base 248 mg 3 times daily
Change in Six Minutes Walking Distance Test; Distance at 6 Minutes (6MWD)	-17.2 meters Standard Deviation 61.06

SECONDARY outcome

Timeframe: Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).

Population: Patients in the modified intention-to-treat population with data for the Modified Timed Up and Go (mTUG) at the early termination visit

The Modified Timed Up and Go (mTUG) measures the patient's ability to get up from a chair (allowing patients to use their arms), walk 3 meters, turn around, walk back to the chair, and sit down. The use of nearby walls or assistance from a caregiver was not allowed.

After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively.

Outcome measures

Measure	Arimoclomol (Open-label) n=61 Participants Arimoclomol base 248 mg 3 times daily
Change in Modified Timed Up and Go (mTUG)	-0.027 meters/second Standard Deviation 0.0847

SECONDARY outcome

Timeframe: Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).

Population: Patients in the modified intention-to-treat population with data for the Quadriceps Muscle Strength at the early termination visit

Maximal voluntary isometric contraction testing (MVICT) of the patient's quadriceps muscle (extensor strength of the knee) were performed using a hand myometer which is a hand-held device that allows the examiner to push against a muscle while the patient resists. The test was performed on each side. The results for the stronger knee are reported here.

After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively.

Outcome measures

Measure	Arimoclomol (Open-label) n=59 Participants Arimoclomol base 248 mg 3 times daily
Change in Quadriceps Muscle Strength	-0.48 kg Standard Deviation 3.719

SECONDARY outcome

Timeframe: Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks).

Population: Patients in the modified intention-to-treat population with data for the Hand Grip Strength test at the early termination visit

Hand grip strength was assessed using a dynamometer. The test was performed on each hand. The grip strength of the stronger hand is reported here.

After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively.

Outcome measures

Measure	Arimoclomol (Open-label) n=65 Participants Arimoclomol base 248 mg 3 times daily
Change in Hand Grip Strength	-0.23 kg Standard Deviation 4.616

SECONDARY outcome

Timeframe: Change from Baseline in IBM-OLE to Early Termination Visit

Population: Since the double-blind lead-in trial (NCT02753530) did not meet any of its efficacy endpoints, the open-label extension trial was terminated prematurely, and the statistical analysis plan (SAP) was amended prior to database lock to align with the focus on safety recommended by FDA (Guidance for Industry: Submission of Abbreviated Reports and Synopses in Support of Marketing Applications). The amended SAP pre-specified that the SF-36 data would not be analyzed since it has no relevance to safety.

The 36-Item Short Form Health Survey (SF-36) is a 36-item, patient-reported survey of health status.

After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol. No derived scores were calculated for SF-36 and no summary tabulation was done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Early Termination Visit

Population: Since the double-blind lead-in trial (NCT02753530) did not meet any of its efficacy endpoints, the open-label extension trial was terminated prematurely, and the statistical analysis plan (SAP) was amended prior to database lock to align with the focus on safety recommended by FDA (Guidance for Industry: Submission of Abbreviated Reports and Synopses in Support of Marketing Applications). The amended SAP pre-specified that the falls data would not be analyzed since it has no relevance to safety.

Patients recorded the number of falls and near falls in a falls diary. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol. No tabulation of falls and near falls was performed.

Outcome measures

Outcome data not reported

Adverse Events

Arimoclomol (Open-label)

Serious events: 13 serious events

Other events: 97 other events

Deaths: 2 deaths

Serious adverse events

Measure	Arimoclomol (Open-label) n=121 participants at risk Arimoclomol base 248 mg 3 times daily
Infections and infestations Corona virus infection	1.7% 2/121 • Number of events 2 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Infections and infestations Pneumonia	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Investigations Transaminases increased	1.7% 2/121 • Number of events 2 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Investigations Electrocardiogram abnormal	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Gastrointestinal disorders Crohn's disease	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Gastrointestinal disorders Large intestine perforation	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
General disorders Disease progression	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Metabolism and nutrition disorders Malnutrition	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Renal and urinary disorders Tubulointerstitial nephritis	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Reproductive system and breast disorders Prostatitis	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Vascular disorders Hypertension	0.83% 1/121 • Number of events 1 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.

Other adverse events

Measure	Arimoclomol (Open-label) n=121 participants at risk Arimoclomol base 248 mg 3 times daily
Injury, poisoning and procedural complications Contusion	5.8% 7/121 • Number of events 9 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Investigations Transaminases increased	8.3% 10/121 • Number of events 10 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Investigations Aspartate aminotransferase increased	10.7% 13/121 • Number of events 13 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Investigations Blood lactate dehydrogenase increased	5.8% 7/121 • Number of events 7 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Investigations Gamma-glutamyltransferase increased	8.3% 10/121 • Number of events 11 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Investigations Alanine aminotransferase increased	11.6% 14/121 • Number of events 14 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Gastrointestinal disorders Diarrhoea	10.7% 13/121 • Number of events 15 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Gastrointestinal disorders Constipation	12.4% 15/121 • Number of events 15 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Gastrointestinal disorders Abdominal discomfort	5.8% 7/121 • Number of events 7 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Psychiatric disorders Insomnia	7.4% 9/121 • Number of events 9 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Gastrointestinal disorders Nausea	6.6% 8/121 • Number of events 10 • Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks). The safety population included all participants who received any amount of study medication in IBM-OLE. At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions. Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.

Additional Information

Medical Affairs

Zevra Denmark A/S

Phone: +1-888-289-5607

Email: medicalaffairs@zevra.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60